Introduction
Clinical experience with photorefractive keratectomy (PRK) since its initial U.S. Food and Drug Administration (FDA) approval in 1995 has confirmed the safety and efficacy of the procedure in treating low to moderate amounts of myopia. Studies have found that an increased ablation-zone diameter of 6 mm offers greater predictability, less hyperopic shift during the first month postoperatively, and less incidence of subepithelial haze. In addition, the larger ablation zone has been associated with fewer patient complaints of halos and poor night vision. This discussion reviews the preclinical and clinical studies of PRK and important conclusions that can be drawn from the human trials.
Preclinical Studies
Using a 193-nm excimer laser, surgeons can precisely etch the cornea and cause minimal adjacent damage. The 193-nm argon-fluorine gas mixture is believed to directly disrupt peptide bonds.1 The laser energy is converted to heat with minimal thermal injury to the adjacent tissue. Presumably, this is attributable to the highly specific and effective photon absorption and the speed of the photoablation process.
A study involving monkey and rabbit models found rapid and stable reepithelialization following excimer laser ablation. After injury, the epithelium must synthesize and assemble the basement membrane and anchoring fibril network necessary for the epithelium to adhere tightly to the stroma. After mechanical keratectomy wounding, full reassembly of the adhesion complex required 1 to 2 months in rabbits and 3 months in monkeys.2
Hyperplasia of the healed epithelium in the center of the ablation zone has been widely observed. Hyperplasia reduces the corneal flattening induced by laser ablation, leading to regression of the initial hyperopic shift.
The ablation zone in both rabbits and monkeys is initially clear, but a diffuse reticular haze has been observed over time. This stromal haze is most pronounced at 1 month and then slowly diminishes over 6 months or longer. Both rabbit and monkey models show evidence of new collagen deposition (types III and VII) under the epithelium in the ablation zone. Deposition of new collagen in the new ablation zone may lead to corneal opacification. Some investigators have hypothesized that denervation of the stromal nerves centrally after excimer laser ablation may cause stromal haze.
Reduced stromal transparency and increased light scattering may be due to one or more of the following factors:
- Increased density of keratocytes and fibroblasts, vacuoles, and stromal debris
- Disruption of collagen fibril size, alignment, or spacing
- Abnormality in the type of or density of anterior stromal proteoglycans
- Deposition of new connective tissue
Many of these abnormalities diminish over time, which is consistent with the observed reduction in reticular haze after PRK. Permanent, dense scar formation, on the other hand, is most likely due to new collagen deposition.
Clinical Studies
Generally, corneal haze following PRK is less severe in humans than in animals. It is important to remember that the depth of ablation for myopic correction increases linearly with the dioptric power, but as a square exponential function of the optical zone diameter. Despite the results with animal studies and the early experience suggesting that haze in humans was indeed correlated with ablation depth, difficulties with smaller optical zones became apparent.
Patient complaints about halos and glare under dim illumination after 3-mm diameter ablations and the lack of any margin for error in centering the ablation zone led clinicians to expand the treatment zone to 6 mm or larger. The increased ablation depth associated with larger ablation zones has been well tolerated. In general, moderate to severe haze is associated with higher levels of myopic correction.
Despite limited animal studies and the lack of a large, prospective, well-controlled study, the use of topical steroids after PRK remains controversial. The theoretical desirability of limiting inflammation and wound healing after PRK led most investigators to adopt routine use of topical steroids for many months postoperatively. Later, laboratory studies continued to demonstrate reduction in inflammation, keratocyte activity, and deposition of new collagen in rabbit corneas following PRK when topical corticosteroids were administered.
Retreatment in PRK patients has been performed when wound healing after the initial procedure resulted in anterior stromal scarring, undercorrection, or both. Repeat PRK was performed at least 6 months after primary treatment. Most, if not all, patients showed improvement in uncorrected visual acuity, best-corrected visual acuity, and residual refractive error. Retreatments were less predictable in patients who had greater levels of haze before treatment. Particularly, patients with the most haze prior to retreatment had a 40% rate of overcorrection.
Human Trials
In myopic PRK, the tissue ablation occurs centrally and decreases in the periphery, resulting in a flatter central cornea. The change in corneal dioptric power depends on the diameter of the ablation zone and the depth of the central ablation. This relationship is defined by the formula, AD = S2D/3, where AD is the ablation depth, S is the diameter of the ablation zone, and D is the intended dioptric correction.3 For example, using a 6-mm ablation zone to correct 4 D of myopia requires an ablation depth of 48 µm. Thus, an increase in the ablation diameter results in a deeper ablation depth for a given myopic correction.
In the Summit (Waltham, Mass.) phase III study, 701 eyes with myopia ranging between -1.5 D and -6 D were enrolled with 1-year follow-up data available on 576 eyes.4 The results showed that 90.7% of patients had uncorrected visual acuity of 20/40 or better, and 66.3% of patients had uncorrected visual acuity of 20/20 or better. Seventy-eight percent of patients had a spherical equivalent manifest refraction within 1 D of emmetropia. Fewer than 1% of patients lost two lines of best-corrected visual acuity. In the Visx (Santa Clara, Calif.) FDA study for low myopia, 691 eyes with myopia ranging from -1 D to -6 D were followed for 24 months.5 Eighty-five percent of eyes had visual acuity of 20/40 or better, with 79% of eyes within 1 D of emmetropia. One percent of eyes lost two lines of best-corrected visual acuity.
Several other studies with 12-month or longer follow-up periods have been reported. In these studies, the number of eyes with 20/40 or better visual acuity has ranged from 27% to 100%, with 34% to 100% of eyes within 1 D of emmetropia. The most frequently reported complications were glare, halos, difficulty with night vision, decreased contrast sensitivity, transient increases in intraocular pressure, mild subepithelial haze, and myopic regression. Eyes losing 2 or more lines of best-corrected visual acuity ranged between 0 and 22%.
Conclusion
Several important conclusions can be drawn from these studies. Initially, in an effort to avoid anterior stromal haze and scarring, several investigators used small ablation zones to decrease the depth of stromal ablation. Subsequent studies demonstrated that haze and scarring were not strongly correlated with ablation depth within the range of low to moderate myopia.
Increasing the ablation-zone diameter has resulted in less initial hyperopic shift and subsequent regression in the first month. Focal irregularities of the corneal epithelium have been demonstrated at the margins of the ablation zone 6 or more months after PRK. The smaller zone itself, perhaps in conjunction with the steeper edge at the ablation margin, may stimulate central epithelial hyperplasia. This reduces the initial flattening of the central cornea and consequently causes greater regression. Thus, 6 mm diameter ablations have resulted in greater predictability of PRK and less incidence of subepithelial haze. In addition, the larger ablation zone has been associated with fewer patient complaints of haloes and poor night vision.
Incorporating blend, or transition, areas into the edge of larger ablation zones is being investigated as a technique to further reduce these problems. Most studies have indicated that an increased incidence and severity of haze occurs, as well as loss of best-corrected visual acuity, when treating higher amounts of myopia. Attempts to correct greater amounts of myopia are also associated with decreased predictability and less likelihood of obtaining 20/40 or better uncorrected visual acuity. Most investigators state that the upper limit of PRK is 10 D to 12 D of myopia.
References
1. Srinivasan R, Sutcliffe E. Dynamics of ultraviolet laser ablation of corneal tissue. Ophthalmology. 1987;103:470-471.
2. Gipson IK, Spurr-Michaud SJ, Tisdale AS. Reassembly of the anchoring structures of the corneal epithelium during wound repair in the rabbit. Invest Ophthalmol Vis Sci. 1989;30:425-434.
3. Colliac JP, Shammas HJ. Optics for photorefractive keratectomy. J Cataract Refract Surg. 1993;19:356-363.
4. Thompson KP, Steinert RF, Stulting RD. Photorefractive keratectomy with the Summit excimer laser system: Phase III U.S. results. In: Salz JJ, ed. Corneal Laser Surgery. St. Louis, Mo: CV Mosby; 1995.
5. Seiler T, McDonnell PJ. Excimer laser photorefractive keratectomy. Surv Ophthalmol. 1995;40:89-118.
6. McDonald MB, Steinert RF, Bafna S. Laboratory and clinical studies of excimer laser refractive surgery. In: Wu HK, et al, eds. Refractive Surgery. New York, NY: Thieme, Inc.; 1999.